Boning Up on Breast Cancer and Bone Health

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Maintaining good bone health is imperative for all women, and it requires extra vigilance for women with breast cancer. It's unfortunately not uncommon for breast cancer to spread to the bones, and some of the treatments that keep breast cancer at bay also threaten skeletal health. Dr. Katherine Weilbaecher explains the medical science behind bone metastasis and bone loss, as well as the best ways to treat these conditions.

This program is produced by HealthTalk and is supported through an unrestricted educational grant from Novartis Oncology.

Announcer:
Welcome to this HealthTalk breast cancer education program. Support is provided to HealthTalk through an unrestricted educational grant from Novartis Oncology. We'd like to thank them for their commitment to patient education. The opinions expressed on this program are solely the views of our guests. They are not necessarily the views of HealthTalk, our sponsor or any outside organization. And, as always, please consult your own physician for the medical advice most appropriate for you. Now here's your host, Demetria Chester.

Demetria Chester:
Hello and welcome. A little-known and often silent complication of breast cancer is bone damage. Whether the damage is caused by cancer spreading to the bone or is a consequence of certain cancer medications, women living with breast cancer can take positive steps to protect their bone health. Joining us today to help us understand these bone complications is Dr. Katherine Weilbaecher, an assistant professor of medicine at Washington University School of Medicine in St. Louis. Dr. Weilbaecher's research focuses on the development of new treatments for breast cancer, including breast cancer that has spread to the bones.

Dr. Weilbaecher, there are two types of bone complications that women with breast cancer can face. Tell us first about bone metastasis, or spread of cancer to the bone.

Dr. Katherine Weilbaecher:
For the most part, we do a very good job of treating breast cancer, diagnosing it at its earliest stages when it's just localized to the breast. But sometimes, breast cancer can leave the breast and metastasize to lymph nodes or to other organs. And the most common site of metastasis outside of the breast is the bones. In women who have metastatic breast cancer, 75 percent will have it in the bones.

While most of the time we can treat and catch breast cancer before it metastasizes, sometimes we aren't so lucky, and it does metastasize to the bone. Generally, the first signs of metastasis are pain in the bone and sometimes fracture. This is less common, but it can occur. The most common first sign might be that the bone hurts in a certain location.

Demetria:
How do you treat bone metastasis?

Dr. Weilbaecher:Thankfully, we have many treatments for bone metastasis. The first treatment is to target the cancer, and we can use either chemotherapy or hormone therapy to try to directly kill the cancer cells. Another way that we treat breast-cancer bone metastasis more specifically is if the breast cancer has spread to only one or two spots in the bone, we will use radiation therapy to target and "spot weld" that little area to try to kill the cancer cells.

Another very important treatment that we use for all women that have metastatic breast cancer to bone is bisphosphonates, which are drugs that inhibit osteoclasts, which are the bone-destroying cells in our body. In fact, bisphosphonates such as Zometa [zoledronate] and pamidronate [Aredia] are now standard of care in the treatment of patients who have metastatic breast cancer to bone. These drugs have been very effective at strengthening the bone and preventing some of the damage that cancer can cause in the bone.

The cancer cells in the bone induce our normal cells, or osteoclasts, to break down and destroy bone. This not only weakens the bone, which can cause fracture, but this is a very painful process. These bone-targeted drugs, bisphosphonates, decrease bone pain, strengthen the bones, and help prevent fracture and other complications such as hypercalcemia and spinal cord compression. Just as important as directly killing the cancer cells with chemotherapy and hormone therapy or even local radiation therapy, bisphosphonate therapy is very important in preventing the complications that occur with bone metastasis.

Demetria:Let's talk about the other common bone complication, and that is bone loss caused by cancer treatments. What treatments might lead to bone loss, and who is most commonly affected?

Dr. Weilbaecher:We are recognizing that not only can cancer cells affect and weaken the bone, but some of our treatments that kill the cancer cells can weaken the bone as well. Especially as our patients are living longer and we are becoming more successful at eradicating breast cancer, it is now recognized that we need to pay attention to this complication.

Specifically, therapies to treat breast cancer such as hormone therapies and even chemotherapy can cause a decrease in estrogen levels, and estrogen is a critical factor that keeps our bones strong. We know that after menopause, when estrogen levels go low, women are at particular risk for osteoporosis and losing bone. And we find that likewise, women who are being treated for breast cancer, where we use hormone therapies which decrease estrogen levels, also lose bone mineral and are at-risk for osteoporosis and fracture.

When we use chemotherapy targeted against the breast cancer, sometimes younger women will undergo menopause and have lower estrogen levels, and they will also be at particular risk for bone loss.

The type of breast cancer that a patient has will determine what type of therapies we use. In women who have tumors that express the estrogen receptor, generally we will use treatments that lower estrogen levels. Those patients are particularly at-risk for bone loss associated with anti-hormone therapies and aromatase-inhibitor therapies. Often, however, in patients who have estrogen receptor-negative cancers, we will use chemotherapy. And because chemotherapy can lower your estrogen levels we still must pay attention to the bones because lowering the estrogen level is going to put you more at-risk for bone loss. In general, in patients with tumors that express estrogen receptors, we will use treatments that are a little bit more toxic to the bones, but in almost all of our patients the therapies could, in fact, lower bone density.

Newer therapies that have been developed to treat breast cancers that express the estrogen receptor are called aromatase inhibitors. We had previously been using tamoxifen to target the estrogen receptor, but now we are using aromatase inhibitors. Women who have already undergone menopause have very little ovarian estrogen circulating. However, we all make testosterone, and testosterone gets converted in our bodies to estrogen by an aromatase [an enzyme that converts androgen to estrogen]. Aromatase inhibitors block the conversion of testosterone to estrogen, so women after menopause who are given aromatase inhibitors have very low levels of estrogen. While cancer cells hate this, and this is excellent for the treatment of breast cancer, this does accelerate bone loss and can weaken the bone.

Demetria:Is this bone loss the same as osteoporosis?

Dr. Weilbaecher:Osteoporosis is a situation where you have extremely low bone mineral, and your bones are weak and prone to fracture. Osteoporosis is usually defined by low bone mineral content. Osteoporosis can follow menopause, as we know, and the bone loss associated with hormone therapies and aromatase inhibitors can lead to a weakening of the bone and osteoporosis. If that loss is extreme enough, you will develop what we call osteoporosis, and you have a much higher fracture risk with that situation.

Demetria:
Would you say that it's now standard for all patients on breast cancer treatment to have a test for bone loss?

Dr. Weilbaecher:
That should be standard. Now that we've learned that patients on aromatase inhibitors or young women on chemotherapy are at-risk for bone loss, it is very important at the start of therapy for patients to be monitored using a DEXA scan, which is a bone mineral density scan, to assess their level of bone mineral.

A DEXA scan takes only about five minutes. It's a tiny little X-ray of either your hip or the spine bone, and it simply measures how much calcium is in that little piece of bone that is monitored. It's noninvasive. It doesn't hurt. It's a very low amount of radiation.

It's a very focused little beam, and we can get a tremendous amount of information about how much calcium is actually in your bones. The way that the DEXA scan is read is the amount of calcium that's in your bone as compared to how much calcium an average 30-year-old woman would have in her bone. We look for how far off you are from a 30-year-old woman. The less bone mineral you have, the more at risk you are for fracture.

A couple of issues: For patients that have a lot of osteoarthritis in the spine or the hips, you can get these little bone spurs that can make your bones look like you have more calcium in them than is really true. But for the most part, these scans are an excellent way to monitor bone mineral.

All women are different, and some women might start their breast cancer treatment with very low levels of bone mineral or even osteoporosis. Those women should be receiving care and attention to their skeleton right at the outset. Other women might have extremely strong bones, and while they need to be followed the urgency of immediate intervention is not there. When we're starting a patient on an anti-hormone therapy that we know is going to put them at high risk for bone loss, getting a baseline bone density is an excellent idea.
Demetria:
Because bone loss is a possible issue with these medications, do you initiate any preventative treatment, or do you wait for symptoms or lab test results?

Dr. Weilbaecher:
For women with breast cancer, I always evaluate whether they're getting adequate calcium and vitamin D in their diet. I always encourage weight-bearing because these strengthen the bones. The results of the DEXA will help determine what I do next.

It is not standard of care to give preventative bisphosphonate therapy to everyone who is being treated with an aromatase inhibitor. However, there are several clinical trials for which we are awaiting the results to determine if this should be done. Right now the standard of care is to evaluate bone mineral density for patients who have osteoporosis. It is standard of care to treat those women with an anti-resorptive agent such as a bisphosphonate. For patients who do not have osteopenia or osteoporosis, we would be monitoring them by getting DEXA scans.

If someone is at high risk for osteoporosis, or if they have significant bone loss as monitored by DEXA, we would then initiate the anti-resorptive.

Demetria:
What guidance would you give as far as early warning signs? In addition to weight-bearing exercise, smoking cessation, taking their vitamins, are there things that women should be looking out for?

Dr. Weilbaecher:
Generally, bone loss can be a painless thing. However, you could develop a compression fracture in the vertebral spine, which is extremely painful. Any sudden onset bone pain definitely should alert you to talk to your doctor. Loss of height: taking a height measurement when you come in to see the doctor and if you notice that you're not as tall as you used to be, that can be a sign of the development of osteoporosis.

But those are usually late signs. The most important thing that women can do is to make sure that we're regularly monitoring their bone mineral density. If patients are on an aromatase inhibitor, for at least the first year or two I would follow this every year to make sure that the loss of bone isn't accelerating.

Dr. Weilbaecher, earlier you suggested DEXA scans. What other tests do you use to monitor for bone loss related to treatment?

Dr. Weilbaecher:Sometimes we will get an X-ray of the spine to see how your spine bones line up and if you've lost any height of the spine. That's another way that we can monitor. In terms of laboratory tests, we can monitor bone turnover. That means how active are these osteoclasts, which are the bone-destroying cells, and the osteoblasts, which are the bone-forming cells. We can do a blood and a urine test that give us an idea of that parameter as well. Taken together, we get a picture of how strong your bones are.

Demetria:Once you've discovered that a woman being treated for cancer is actually losing bone, what steps do you take?

Dr. Weilbaecher:If the DEXA scan shows that a patient is severely osteopenic, which means she has a lower amount of calcium in her bone, or osteoporotic, which means she has a very low level of calcium in her bone, the most commonly prescribed treatment would be a bisphosphonate.

There are many different types of bisphosphonates. There are bisphosphonates that are pills, such as Fosamax [alendronate] or Actonel [risedronate], which are commonly used in osteoporosis. There are intravenous bisphosphonates, such as pamidronate or zoledronic acid, which are commonly used in metastatic breast cancer. The use of these drugs has been shown in both osteoporosis studies and in patients with metastatic breast cancer to strengthen the bone, to prevent fractures and to halt further bone loss. So when someone definitely has a low bone mineral on the DEXA scan, the first step would be to administer a bisphosphonate to halt the bone loss.

Demetria:
You would say that these bisphosphonates are fairly effective when it comes to preventing further bone loss?

Dr. Weilbaecher:Yes. In randomized clinical trials, the bisphosphonates have been shown to decrease fractures in women who have osteoporosis, and can also prevent further decline in bone mineral loss. Currently, several clinical trials have been performed in women with breast cancer who are starting aromatase inhibitors, and we are awaiting the results of how well bisphosphonates prevent that bone loss. But given what we know, there's every indication that these will help halt the loss. The key is that it is very hard to rebuild bone, so rather than waiting until patients have lost a lot of bone, to try to intervene early before there's been too much bone loss.

Demetria:Do you see any differences between Aredia [pamidronate] and Zometa [zoledronic acid] as far as effectiveness in breast cancer-related bone loss?

Dr. Weilbaecher:Aredia and Zometa are intravenous bisphosphonates that are very powerful at blocking osteoclasts and preventing bone loss. They have been evaluated in women who have metastatic breast cancer to bone, and they have both been shown to be quite effective at preventing fractures and decreasing bone pain in women who have metastatic breast cancer. Zometa, or zoledronic acid, is more powerful than pamidronate at decreasing osteoclast function. Zoledronic acid is also being evaluated in osteoporosis. These studies have been completed, and the results are being evaluated, looking at how effective it is at preventing bone loss associated with aromatase inhibitors in the treatment of breast cancer, not in the metastatic setting. When these studies come out, we will have excellent information.

Demetria:These injectables, you said they're more powerful. Do they also come with more side effects as well?

Dr. Weilbaecher:In general, bisphosphonates, both oral and IV, are fairly well-tolerated. The intravenous bisphosphonates do have some small side effects, generally well-managed clinically. It has been shown that they could affect kidney function. However, when infused slowly with an adequate amount of hydration, for the most part, in studies we've not seen a tremendous amount of kidney damage. In patients who have abnormal kidney function, it is recommended to decrease the dose of the bisphosphonate and to follow this closely. But if you're following kidney function and given over the appropriate amount of time with an adequate amount of fluid, that risk is fairly small.

Some patients have reported flushing, flulike symptoms after an injection of the intravenous bisphosphonate, which is temporary. Often, this is well-treated with Tylenol [acetaminophen] and may not happen every time. Again, this would be a very rare side effect.

Because the bisphosphonates affect osteoplastic resorption, which is how we regulate our serum calcium levels, some patients have reported symptoms related to a temporary decrease in calcium levels. Again, this would be rare, and, generally, taking oral calcium would help that.

What has gotten some attention recently has been a rare complication, observed in patients taking both intravenous and oral bisphosphonates, called osteonecrosis of the jaw. It's associated with mouth or jaw pain, and exposed bone in the gum. The gum retracts back, and you can see the jaw bone, and this bone is very weakened. The thinking is that patients who have gum and dental disease could be at particular risk for this complication. Patients who are on steroids or who have received radiation to the jaw are also at particular risk. Scientists are trying to understand how this is caused, the risks, the triggers and how can it be treated. Right now, the recommendations are that before patients start an intravenous or oral bisphosphonate, either for osteoporosis or for cancer metastasis to the bone, that patients go the dentist, gum and dental disease is treated, and patients take excellent care of teeth to prevent any dental infections.

Demetria:Overall then, would you say that the benefits outweigh the risk?

Dr. Weilbaecher:Yes, I do.

Demetria:Let's talk briefly about possible future treatments for bone complications. Are there other bisphosphonates in clinical trials that may be available to patients soon?

Dr. Weilbaecher:A number of other approaches are being looked at. Not only are the intravenous bisphosphonates zoledronic acid and pamidronate available, there are oral bisphosphonates such as Fosamax and Actonel or risedronate. And another bisphosphonate that has been used in Europe is now approved in this country, ibandronate [Boniva], which comes both in an oral and an IV form and is being used in patients who have osteoporosis.

In terms of other strategies, there are other osteoclast inhibitor compounds, which can block bone resorption that are being tried in osteoporosis, as well as in cancer treatment-induced bone loss. These are right now in Phase III clinical trials. For example, there is a RANK ligand antibody, which blocks osteoclasts directly. This is a treatment that is being pursued in clinical trials. So I think down the line we're going to have several options for strengthening the bones of patients with osteoporosis, with cancer-induced bone loss and with bone metastasis.

Demetria:Can you share with our audience some practical ways for people living with breast cancer to protect their bone health?

Dr. Weilbaecher:My patients often ask me, "What can I do to improve my chances of beating the cancer and keeping healthy?" From evaluating the research that cancer likes weak bones, anything that you do to strengthen your bones not only keeps your skeleton healthy but also makes your bones less friendly to cancer. Take a good look at how much calcium you get in your diet. We recommend about 1,200 milligrams of calcium, and unless you drink a lot of milk that's hard to get. Often patients need to supplement with calcium supplements.

Vitamin D helps our bodies absorb calcium and put it into the bones, and we get vitamin D really from sunlight. I ask my patients to try to have their skin see the sun for about 20 minutes a day, if possible. And if that's not possible, then take a calcium [supplement] with vitamin D supplement.

In terms of what triggers our bodies to take the calcium from our diet and put it into the bones, exercise is the best inducer of that. Weight-bearing exercise, using your bones and putting pressure on your bones, helps put calcium into them and make them stronger. Walking is outstanding exercise. Take the stairs when possible.

[Here's] another last point. A lot of my patients don't like to take pills - who does? But the best time to take your calcium supplements is at night, just before bedtime, because that's when calcium is most often placed into the bones.

Demetria:Thank you, Dr. Weilbaecher. We've been talking with Dr. Katherine Weilbaecher from Washington University in St. Louis. From all of us at HealthTalk's Breast Cancer Education Network, I'm Demetria Chester. We wish you and your family the very best of health.

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